A stent is a generally longitudinal tubular device formed of biocompatible material, preferably a metallic or plastic material. Stents are useful in the treatment of stenosis, strictures or aneurysms in body vessels, such as blood vessels. It is well-known to employ a stent for the treatment of diseases of various body vessels. The device is implanted either as a “permanent stent” within the vessel to reinforce collapsing, partially occluded, weakened or abnormally dilated sections of the vessel or as a “temporary stent” for providing therapeutic treatment to the diseased vessel. Stents are typically employed after angioplasty of a blood vessel to prevent restenosis of the diseased vessel. Stents may be useful in other body vessels, such as the urinary tract and the bile duct.
A typical stent includes an open flexible configuration. The stent configuration allows the stent to be configured in a radially compressed state for intraluminal catheter insertion into an appropriate site. Once properly positioned within the lumen of a damaged vessel, the stent is radially expanded to support and reinforce the vessel. Radial expansion of the stent may be accomplished by an inflatable balloon attached to the catheter, or the stent may be of the self-expanding type that will radially expand once deployed. An example of a suitable stent is disclosed in U.S. Pat. No. 4,733,665, which is incorporated herein by reference in its entirety.
Stents find various uses in surgical procedures. For instance, stents are widely used in angioplasty. Angioplasty involves insertion of a balloon-tipped catheter into an artery at the site of a partially obstructive atherosclerotic lesion. Inflation of the balloon can rupture the intima and media, dramatically dilating the vessel and relieving the obstruction. About 20 to 30% of obstructions reocclude in a few days or weeks, but most can be redilated successfully. Use of stents significantly reduces the reocclusion rate. Repeat angiography one year after angioplasty reveals an apparently normal lumen in about 30% of vessels on which the procedure has been performed.
Angioplasty is an alternative to bypass surgery in a patient with suitable anatomic lesions. The risk is comparable with that of surgery. Mortality is 1 to 3%; myocardial infarction rate is 3 to 5%; emergency bypass for intimal dissection with recurrent obstruction is required in <3%; and the initial success rate is 85 to 93% in experienced hands.
Stents are also used in percutaneous endovascular therapy. Many new treatments for vascular disease (occlusions and aneurysms) avoid open surgery. These treatments may be performed by interventional radiologists, vascular surgeons, or cardiologists. The primary approach is percutaneous translumninal angioplasty (PTA), whereby a small high-pressure balloon is used to open an obstructed vessel. However, because of the high recurrence rate of obstruction, alternative methods may be necessary.
A stent, such as a metallic mesh-like tube, is generally inserted into a vessel at an obstructed site. As stents can be very strong, they tend to keep vessels open much better than balloons alone. Moreover, the recurrence rate of obstruction is reportedly lower when stents are used. Stents work well in larger arteries with high flow, such as iliac and renal vessels. They work less well in smaller arteries, and in vessels in which the occlusions are long. Stents for carotid disease are being studied.
There are at least two known causes of post-operative restenosis—elastic recoil, wherein the vessel contracts due to the natural elasticity of the vessel walls, and neointimal hyperplasia, wherein medial cells proliferate in response to immune system triggers. Stents have proven useful in reducing the incidence and/or severity of post-operative elastic recoil restenosis, as they resist the tendency of blood vessels to restenose after removal of the balloon. Stents have proven less useful for treatment of neointimal hyperplasia, which arises out of a complex immune response to expanding and fracturing the atherosclerotic plaque. In the case of neointimal hyperplasia, the initial expansion and fracture of the atherosclerotic lesion initiates inflammation, which gives rise to a complex cascade of cellular events that activates the immune system, which in turn gives rise to the release of cytokines that stimulate cell multiplication in the smooth muscle layers of the vessel media. This cell stimulation eventually causes the vessel to restenose.
Various approaches to the problem of neointimal hyperplasia have been attempted. Among these approaches are: subsequent stent placement, debulking, repeat angioplasty, and laser treatment. Another recent approach has been to coat the stent with an immunosuppressant or a chemotherapeutic drug. Immunosuppressant drugs, such as rapamycin, target cells in the G1 phase, preventing initiation of DNA synthesis. Chemotherapeutic drugs, such as paclitaxel (Taxol—Bristol-Myers Squibb) and other taxane derivatives, act on cells in the M phase, by preventing deconstruction of microtubules, thereby interrupting cell division. While these approaches present some promise, they also suffer certain limitations, such as the tendency for rapamycin and taxanes to quickly disperse from the stent site, thereby both limiting the drugs' effective duration in proximity to the stent and also risking undesirable systemic toxic effects.
There is therefor a need for an improved stent that will provide sustained-release of pharmaceutically active compounds, such as immunosuppressant, antiproliferative, chemotherapeutic, and anti-inflammatory drugs, at or near the site of stent implantation that alleviates or avoids the problem of rapid depletion of drug from the stent site. There is also a need for an improved drug that may be employed in such a stent.
There is furthermore a need for an improved stent that will provide sustained-release of pharmaceutically active compounds, such as immunosuppressant, chemotherapeutic, and anti-inflammatory drugs, at or near the site of stent implantation that does not suffer the drawbacks of causing systemic toxic effects of the immunosuppressant, chemotherapeutic, and anti-inflammatory drugs. There is also a need for an improved drug that may be employed in such a stent.